Genetic variants of phosphoglucose isomerase were purified from mouse and Drosophila by 8-(6-aminohexyl)-amino-ATP-Sepharose-column followed by preparative isolectric focusing. Antisera were raised for purified mouse and Drosophila enzymes in rabbits. A null variant of phosphoglucose isomerase identified in natural populations of Drosophila was shown to produce no proteins that cross-react with the antiserum specific to this enzyme (CRM-negative).